F. Mignon

Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression

Background. The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. Methods. This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1–2 mg/kg per day. Results. At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P =0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P =0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P =0.009), leukopenia (37.3% vs. 9.5%, P <0.001), fever (25.2% vs. 10.1%, P =0.001), herpes simplex (17.9% vs. 5.7%, P =0.001), and thrombocytopenia (11.3% vs. 3.2%, P =0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction). Conclusion. Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.

A three-arm study comparing immediate tacrolimus therapy with antithymocyte globulin induction therapy followed by tacrolimus or cyclosporine A in adult renal transplant recipients.

Background. Induction therapy with antithymocyte globulin (ATG) reduces the incidence of acute rejection after transplantation. A study was undertaken to assess the efficacy and safety of ATG induction on tacrolimus-based and cyclosporine A (CsA)-based therapies compared with immediate tacrolimus triple therapy in kidney transplant recipients. Methods. In a 6-month, open-label, randomized, prospective study conducted in 30 European centers, 555 renal transplant patients were randomly assigned to tacrolimus triple therapy (Tac triple, n=185), ATG induction with tacrolimus (ATG-Tac, n=186), or ATG induction with CsA microemulsion (ATG-CsA, n=184); all were combined with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection episode confirmed by biopsy. Results. Patient demographics and clinical parameters at baseline were similar. Patient and graft survival rates were similar in all groups. The incidence of clinically apparent acute rejection was significantly higher (P =0.003) for Tac triple (33.0%) compared with ATG-Tac (22.6%) and the incidence for ATG-Tac was significantly lower (P =0.004) than for ATG-CsA (37.0%). The incidences of acute rejection confirmed by biopsy (primary endpoint) were 25.4%, 15.1%, and 21.2% for Tac triple, ATG-Tac, and ATG-CsA, respectively (Tac triple vs. ATG-Tac, P =0.004). The incidences of corticosteroid-resistant acute rejection were 7.0% (Tac triple), 4.8% (ATG-Tac), and 10.9% (ATG-CsA) (ATG-Tac vs. ATG-CsA, P =0.038). In the ATG groups, the incidences of leukopenia, thrombocytopenia, serum sickness, fever, and cytomegalovirus infection were significantly higher (P <0.05). Conclusions. Acute rejection was significantly lower in the ATG-Tac group compared with the ATG-CsA and Tac triple groups. Significantly more hematologic and infectious adverse events were observed in both ATG induction groups.

The influence of automated peritoneal dialysis on the decrease in residual renal function.

BACKGROUND Automated peritoneal dialysis (APD) has been increasingly used in recent years. Our purpose was to investigate whether the good preservation of residual renal function (RRF) that has been reported in patients on continuous ambulatory peritoneal dialysis (CAPD) is also observed in APD. METHODS RRF was determined and compared prospectively over 1 year in two groups of peritoneal dialysis (PD) patients: 18 consecutive new patients starting on APD (12 continuous cyclic peritoneal dialysis (CCPD) patients and six nightly intermittent peritoneal dialysis (NIPD) patients) and 18 selected patients who had started on CAPD at the same time and were matched for baseline characteristics. RRF was assessed on normalized creatinine clearance (ml/min/1.73 m2) measured before the start of PD, at 6 months, and at 1 year. Wilcoxons rank sum test was used to compare differences between the two groups. RESULTS Creatinine clearance (ClCr) was 6.1 ml/min in the APD group and 6 ml/min in the CAPD group at the start of PD. The monthly rate of ClCr decrease was significantly higher in the APD group: -0.28 ml/min vs -0.1 ml/min (P = 0.04) at 6 months and -0.26 ml/min vs -0.13 ml/min (P = 0.005) at 1 year. RRF decreased at the same rate in patients treated with NIPD or CCPD. The daily instilled volume of 3.86% glucose dialysis solution (l/day) was higher in APD patients than in CAPD patients: 2.5 vs 0 at 6 months and 1 year but there was no significant difference in ultrafiltration rate (l/day) between APD and CAPD patients at these timepoints: 0.53 vs 0.6 and 0.88 vs 0.7 respectively. There was no difference between the two groups in body weight and blood pressure, which remained stable in both groups throughout the study period. CONCLUSIONS RRF declined rapidly in APD patients whereas it was well preserved in CAPD patients. This may be explained by the less stable fluid and osmotic load together with the intermittent nature of APD and the larger use of hypertonic dialysate. RRF should be closely monitored in APD patients in order to adjust PD prescriptions and maintain adequacy.

Fungal Peritonitis in Patients on Peritoneal Dialysis

Fungal peritonitis (FP) is a serious complication of peritoneal dialysis, both in terms of morbidity and mortality. Available data on the effectiveness of fluconazole in eradicating FP without catheter removal are still controversial. We reviewed 20 FP cases that occurred among 325 patients who underwent peritoneal dialysis in our center between January 1984 and January 1992, in order to establish whether a profile of patients at risk of developing FP could be identified and to evaluate the effectiveness of fluconazole in treating FP (7 cases). Age, sex, a particular cause of end-stage renal disease, and the presence of diabetes did not correlate significantly with the development of FP. The risk of FP increased in patients on immunosuppressive treatment. Sixteen of our 20 patients had bacterial peritonitis during the month before they developed FP. Nineteen were treated with antibiotics. Neither the type of bacterial organism isolated during the bacterial peritonitis preceding FP nor modality and duration of antibiotic treatment correlated significantly with the development of FP. Patients who subsequently developed FP were more frequently treated with antibiotics while in hospital (p < 0.001). Candida species accounted for 15 of our 20 FP cases (75%), with Candida albicans being by far the most common isolate. Treatment strategies varied among the 20 patients. The combination of intravenous or intraperitoneal administration of 5-fluorocytosine and oral administration of fluconazole was used in 7 cases: only 1 patient was cured without catheter removal, 1 patient died within the first 4 days of treatment, removal of peritoneal catheter was necessary in the other 5 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Didanosine pharmacokinetics in patients with normal and impaired renal function: influence of hemodialysis.

The pharmacokinetics of didanosine were investigated following oral administration of a single 375-mg dose to eight human immunodeficiency virus-seropositive patients with normal renal function and eight human immunodeficiency virus-seropositive uremic patients. In uremic patients, the plasma half-life was longer than that in control patients (respectively, 4.5 +/- 2.2 and 1.6 +/- 0.4 h). The ratio of total plasma clearance to absolute bioavailability was four- to fivefold lower in uremic patients than in patients with normal renal function (respectively, 491 +/- 181 and 2,277 +/- 738 ml/min). Because of the decrease in elimination, concentrations in plasma were higher for uremic patients than for control patients; the maximum concentrations of drug in plasma were, respectively, 3,978 +/- 1,607 and 1,948 +/- 994 ng/ml; the areas under the concentration-time curve were, respectively, 14,050 +/- 4,262 and 3,000 +/- 956 ng.h/ml. Didanosine was removed by hemodialysis with an extraction ratio of 53% +/- 8%, a hemodialysis clearance value of 107 +/- 21 ml/min, and a fractional drug removal during a 4-h dialysis of 20% +/- 8% of the dose. Dosage adjustments are necessary in uremic patients.

Effects of Long-Term Treatment with Recombinant Human Erythropoietin on Physiologic Inhibitors of Coagulation

Recombinant human erythropoietin (rHu-EPO) in the treatment of renal anemia might predispose to an increased risk of thrombotic complications. In an attempt to comprehend the involvement of the physiologic inhibitors of coagulation in this process, we studied 2 groups of hemodialysis patients. Group I included 21 patients receiving a starting dose of 90 IU/kg/week s.c., and group II included 17 patients without rHu-EPO. The following coagulation tests were performed before rHu-EPO treatment, and after 1, 6 and 12 months: prothrombin time; activated partial fistula thromboplastin time; fibrinogen; plasminogen activity; antithrombin III activity; protein C activity; total and free protein S antigens, and C4b binding protein. Only the latter three parameters were changed in group 1, while high baseline levels of protein S antigens were found in both groups. A decrease in total and free protein S was observed within 1 month of treatment. At the 6th month total protein S returned to near pretreatment values, whereas a significant fall in free protein S (p = 0.007) was observed. All three parameters returned to near baseline values by 12 months. These results suggest that protein S activity can be altered at the beginning of EPO therapy, a change that under favoring circumstances might contribute to the thrombotic events reported during the early phase of rHu-EPO treatment.

Failing arteriovenous hemodialysis fistulas: assessment with magnetic resonance angiography.

RATIONALE AND OBJECTIVES The authors sought to evaluate prospectively magnetic resonance angiography (MRA) versus fistulography in the detection and characterization of complications associated with malfunctioning hemodialysis access fistulas (arteriovenous fistulas [AVF]). METHODS Nineteen patients with clinical AVF dysfunction were studied by MRA and fistulography. Data from each study were collected prospectively and analyzed in a blinded manner. RESULTS The main diagnosis was stenosis in eight patients, thrombosis in five patients (mural thrombosis with preserved flow in one), aneurysm without stenosis in two patients, and normal AVF in four patients. A hazy flow void, assumed to be related to turbulence, was observed in normal arterial anastomoses. When flow void was considered as a criterion of stenosis or thrombosis, one false-positive and one false-negative MRA study were determined, yielding a sensitivity and specificity of 92% and 86%, respectively. CONCLUSIONS Magnetic resonance angiography is a feasible and sensitive technique with which to portray suspected malfunctioning hemodialysis access fistulas.

AA amyloidosis in systemic lupus erythematosus: an unusual complication

a nephrotic syndrome. The only SLE activity she Introduction reported during this time were brief episodes of polyarthralgia. Laboratory tests showed a normal creatinAA amyloidosis is a complication of chronic inflamine level, albumin concentration at 1.79 g/dl, heavy matory diseases including Crohn’s disease, rheumatoid proteinuria (3 g/day), no haematuria, antinuclear antiarthritis, ankylosing spondylitis, and juvenile rheumatbody titres of 1/500, no anti-DNA antibodies, no oid arthritis. In contrast to the past, today it is less monoclonal gammopathy, and normal levels of comfrequently associated with chronic infectious diseases plement factors. The CRP level was high (6.7 mg/dl ) such as tuberculosis. AA amyloidosis has also been despite the presence of a nephrotic syndrome. No reported in cancer, Muckle–Wells disease and familial infectious disease was found. Although there were no Mediteranean fever (FMT) where the incidence differs signs of active SLE, a diagnosis of membranous between less than 10% for Armeniens and Arabs and glomerulopathy was entertained and renal biopsy was over 30% among Turks and Sephardic Jews. performed which revealed massive glomerular and Conversely, AA amyloidosis is not a classic comvascular Congo-red-positive areas exhibiting green plication of SLE, and fewer than 20 cases have been birefringence under polarized light, staining with reported in English worldwide, although cases of SLE anti-AA antibodies but not with other sera (Figure 1). with monoclonal gammopathy may be complicated by Optic microscopy and immunofluorescence study AL amyloidosis. detected no SLE nephritis. Electron-microscopic We observed one unusual patient with SLE analysis was not performed. complicated by AA amyloidosis. The patient received colchicine (1 mg/day). Subsequently, clinical and biological findings suggested hepatic and intestinal amyloid involvement. Renal Case insufficiency began 2 months later and progressed in 6 months to end-stage renal disease; the patient was then A 55-year-old woman with a 4-year history of SLE without renal involvement was admitted with a nephrotic syndrome. SLE had been diagnosed when she was 51 years old, following a 10-year history of isolated dermatological problems: she presented with non-destructive and non-deforming polyarthritis, skin rash, and iliac thrombophlebitis. Laboratory investigation revealed high titres of antinuclear (1/1000) and anti-DNA (82 U/ml ) antibodies. There was no haematuria, no proteinuria, the creatinine level was normal, and the C-reactive protein level (CRP) was very high (3.6 mg/dl ); lupus anticoagulant and IgG anticardiolipid (34 U GPL) were also present. She met four of the American Rheumatism Association’s criteria for SLE, and was treated with oral corticosteroid. She was readmitted to our service 4 years later with

Upper limb vein anatomy before hemodialysis fistula creation: cross-sectional anatomy using MR venography.

Abstract. Preoperative imaging is indicated to discriminate patent, adequate superficial veins of the upper limbs undetectable by clinical inspection that could be anastomosed for the creation of a durable and functional hemodialysis fistula. The aim of this pictorial review is to provide a venous anatomic map of the upper limbs using MR venography (MRV) which could help surgeons before creation of hemodialysis access fistulas (AVF). At the level of the forearm, the antebrachial cephalic vein is the most commonly identified as patent. At the level of the elbow and distal arm, the cephalic vein is patent in 80% of normal subjects, and less often patent (23–26%) than basilic vein (33–38%) in patients. Overall, reading transaxial MR views can help for assessing upper limb vein anatomy before creation of a hemodialysis access fistula.

Effect of Recombinant Human Erythropoietin on Nutritional Status and Plasma Lipids in Uremic Patients

Dr. Béatrice Viron, Service de Néphrologie, Hôpital Tenon, 4, rue de la Chine, F-75020 Paris (France) Dear Sir, Improved appetit and food intake have been reported from earlier studies of patients treated with recombinant human erythro-poietin (r-Hu EPO) [1]. An increase in BUN, plasma creatinine and plasma phosphorus values as well as, in some cases, severe hyper-kaliemia were observed in certain series [2]. Contrasting with their generally poor nutritional status [3], plasma lipid abnormalities are common in uremic patients [4], especially those maintained on hemodialysis (HD) or peritoneal dialysis (PD). In those patients, particularly prone to diffuse atherosclerosis [5], any deleterious effect of r-Hu EPO on plasma lipids might question the benefit of correcting anemia with this treatment. However, the effect on plasma lipids of the r-Hu-EPO-induced changes concerning the nutritional behavior of uremic patients had not been assessed yet. We have studied 12 patients, 7 HD (4 males, 3 females, mean age 57) and 5 PD (3 males, 2 females, mean age 70). Plasma lipids were measured together with different reliable parameters of the nutritional status [3], first, before initiating r-Hu EPO, then 6 months from the date of correction of anemia (defined as Hb > 10 g/dl). The following data were collected: body mass index, triceps skin-fold thickness (TST), arm muscle circumference (AMC), serum albumin, prealbumin, transferrin, total cholesterol, triglycerides (Tg), apolipoprotein (Apo) Al, Apo B, retinol-binding protein and acid αΓglycopro-tein. These values were compared to those obtained from 7 HD and 12 PD nonanemic patients, matched for age, sex and duration of maintenance dialysis. Before EPO, Hb was 7.2 ± 0.4 g/dl in the HD and 8.6 ± 0.7 g/dl in the PD patients. The PD patients had decreased serum albumin (2.9 ± 0.4 g/dl), increased Tg (2.3 ± 1.4 mmol/ 1) and Apo B (0.16 ± 0.05 g/dl), whereas only Tg were abnormally high (2.0 ± 1.1 mmol/l) in HD patients. However, anthropometric hallmarks of malnutrition were exclusively found in male HD patients, who had low values of body mass index (20.9 ± 1.0 kg/m2), TST (4.2 ± 1.1 mm) and AMC (22.4 ± 2.7 cm). After 6 months with stable Hb (HD: 10.4 ± 0.8 g/dl; PD: 10.1 ± 0.6 g/dl), only the male HD patients exhibited a significant increase in TST (5.1 ± 1.2 mm; p < O.Ol) and AMC (23.1 ±